tbuckley/cabot-search huggingface dataset:
Detection of left ventricular systolic dysfunction from single-lead electrocardiography adapted for portable and wearable devices
Authors: Akshay Khunte, Veer Sangha, Evangelos K. Oikonomou, Lovedeep S. Dhingra, Arya Aminorroaya, Bobak J. Mortazavi, Andreas Coppi, Cynthia A. Brandt, Harlan M. Krumholz, Rohan Khera
Journal: npj Digital Medicine (2023)

Artificial intelligence (AI) can detect left ventricular systolic dysfunction (LVSD) from electrocardiograms (ECGs). Wearable devices could allow for broad AI-based screening but frequently obtain noisy ECGs. We report a novel strategy that automates the detection of hidden cardiovascular diseases, such as LVSD, adapted for noisy single-lead ECGs obtained on wearable and portable devices. We use 385,601 ECGs for development of a standard and noise-adapted model. For the noise-adapted model, ECGs are augmented during training with random gaussian noise within four distinct frequency ranges, each emulating real-world noise sources. Both models perform comparably on standard ECGs with an AUROC of 0.90. The noise-adapted model performs significantly better on the same test set augmented with four distinct real-world noise recordings at multiple signal-to-noise ratios (SNRs), including noise isolated from a portable device ECG. The standard and noise-adapted models have an AUROC of 0.72 and 0.87, respectively, when evaluated on ECGs augmented with portable ECG device noise at an SNR of 0.5. This approach represents a novel strategy for the development of wearable-adapted tools from clinical ECG repositories.
Nanopore sequencing technology and its applications
Authors: Peijie Zheng, Chuntao Zhou, Yuemin Ding, Bin Liu, Liuyi Lu, Feng Zhu, Shiwei Duan
Journal: MedComm (2023)

Abstract Since the development of Sanger sequencing in 1977, sequencing technology has played a pivotal role in molecular biology research by enabling the interpretation of biological genetic codes. Today, nanopore sequencing is one of the leading third‐generation sequencing technologies. With its long reads, portability, and low cost, nanopore sequencing is widely used in various scientific fields including epidemic prevention and control, disease diagnosis, and animal and plant breeding. Despite initial concerns about high error rates, continuous innovation in sequencing platforms and algorithm analysis technology has effectively addressed its accuracy. During the coronavirus disease (COVID‐19) pandemic, nanopore sequencing played a critical role in detecting the severe acute respiratory syndrome coronavirus‐2 virus genome and containing the pandemic. However, a lack of understanding of this technology may limit its popularization and application. Nanopore sequencing is poised to become the mainstream choice for preventing and controlling COVID‐19 and future epidemics while creating value in other fields such as oncology and botany. This work introduces the contributions of nanopore sequencing during the COVID‐19 pandemic to promote public understanding and its use in emerging outbreaks worldwide. We discuss its application in microbial detection, cancer genomes, and plant genomes and summarize strategies to improve its accuracy.
Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study
Authors: Pauline Lemmens, Edouard Louis, Wouter Van Moerkercke, Lieven Pouillon, Michael Somers, Harald Peeters, Stijn Vanden Branden, Julie Busschaert, Filip Baert, Anneline Cremer, Philippe Potvin, Sophie Dewit, Arnaud Colard, Jo Swinnen, Guy Lambrecht, Christophe Claessens, Barbara Willandt, Pieter Dewint, Evi Van Dyck, Joao Sabino, Séverine Vermeire, Marc Ferrante
Journal: Clinical Gastroenterology and Hepatology (2023)
Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies
Authors: Ziyu Ji, Jianlin Shen, Yujian Lan, Qian Yi, Huan Liu
Journal: MedComm (2023)

Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant bone tumors. Neoadjuvant chemotherapy combined with limb-preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases and OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management of OS. There has been an urgent need to identify new biomarkers for OS to develop specific targeted therapies. Recently, the continued advancements in genomic analysis have contributed to the identification of clinically significant molecular biomarkers for diagnosing OS, acting as therapeutic targets, and predicting prognosis. Additionally, the contemporary molecular classifications have revealed that the signaling pathways, including Wnt/β-catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD-1/PD-L1, MAPK, and NF-κB, have an integral role in OS onset, progression, metastasis, and treatment response. These molecular classifications and biological markers have created new avenues for more accurate OS diagnosis and relevant treatment. We herein present a review of the recent findings for the modulatory role of signaling pathways as possible biological markers and treatment targets for OS. This review also discusses current OS therapeutic approaches, including signaling pathway-based therapies developed over the past decade. Additionally, the review covers the signaling targets involved in the curative effects of traditional Chinese medicines in the context of expression regulation of relevant genes and proteins through the signaling pathways to inhibit OS cell growth. These findings are expected to provide directions for integrating genomic, molecular, and clinical profiles to enhance OS diagnosis and treatment.
Bioreducible exosomes encapsulating glycolysis inhibitors potentiate mitochondria-targeted sonodynamic cancer therapy via cancer-targeted drug release and cellular energy depletion
Authors: Thuy Giang Nguyen Cao, Quan Truong Hoang, Ji Hee Kang, Su Jin Kang, Vasanthan Ravichandran, Won Jong Rhee, Minjong Lee, Young Tag Ko, Min Suk Shim
Journal: Biomaterials (2023)
Clinical features and genomic landscape of myeloproliferative neoplasm (MPN) patients with autoimmune and inflammatory diseases (AID)
Authors: Dikelele Elessa, Lin-Pierre Zhao, Rafael Daltro de Oliveira, Nabih Maslah, Juliette Soret-Dulphy, Emmanuelle Verger, Clémence Marcault, Nathalie Parquet, Pierre Fenaux, Lionel Adès, Emmanuel Raffoux, Stéphane Giraudier, Olivier Fain, Bruno Cassinat, Jean-Jacques Kiladjian, Arsene Mekinian, Lina Benajiba
Journal: Leukemia (2023)
Anaplastic large cell lymphoma in people with breast implants
Authors: Christie Brennan, Alexandra Moorhouse, Roxane Vermeland, Peter Kneeshaw
Journal: BMJ (2023)

What you need to know How do patients present? (fig 1)This is one of a series of occasional articles to help doctors prevent, diagnose, and respond to adverse drug reactions that may be serious if not recognised.The article describes an adverse reaction that can occur in response to a medical device rather than a drug; however, advisers to the Adverse drug reaction series felt this was a suitable topic to cover.
Omega-3 polyunsaturated fatty acids in sarcopenia management: A network meta-analysis of randomized controlled trials
Authors: Ping-Tao Tseng, Bing-Yan Zeng, Bing-Syuan Zeng, Yu-Chi Liao, Brendon Stubbs, John S. Kuo, Cheuk-Kwan Sun, Yu-Shian Cheng, Yen-Wen Chen, Tien-Yu Chen, Yu-Kang Tu, Pao-Yen Lin, Chih-Wei Hsu, Dian-Jeng Li, Chih-Sung Liang, Mein-Woei Suen, Yi-Cheng Wu, Yow-Ling Shiue, Kuan-Pin Su
Journal: Ageing Research Reviews (2023)
Tumor Necrosis Factor Inhibitors in Inflammatory Bowel Disease and Risk of Immune Mediated Inflammatory Diseases
Authors: Daniel Ward, Nynne Nyboe Andersen, Sanne Gørtz, Aske Thorn Iversen, Kristine Højgaard Allin, Laurent Beaugerie, Julien Kirchgesner, Tine Jess
Journal: Clinical Gastroenterology and Hepatology (2023)
Role of blaTEM and OmpC in the piperacillin-tazobactam resistance evolution by E. coli in patients with complicated intra-abdominal infection
Authors: Lydia Gálvez-Benítez, José Manuel Ortiz de la Rosa, Angel Rodriguez-Villodres, Carlos S. Casimiro-Soriguer, Irene Molina-Panadero, Rocío Alvarez-Marin, Rémy A. Bonnin, Thierry Naas, Jerónimo Pachón, José Miguel Cisneros, José Antonio Lepe, Younes Smani
Journal: Journal of Infection (2023)

Piperacillin-tazobactam resistance (P/T-R) is increasingly reported among Escherichia coli isolates. Although in vitro experiments have suggested that blaTEM gene plays a key role in the P/T-R acquisition, no clinical in vivo study has yet confirmed the role of blaTEM or other genes. Therefore, we aimed to identify the mechanisms underlying P/T-R by following up patients with E. coli complicated intra-abdominal infections (cIAI) who experienced P/T treatment failure. Four pairs of strains, clonally related from four patients, were isolated both before and after treatment with P/T dosed at 4 g/0.5 g intravenously. The P/T MIC was tested using broth microdilution, and β-lactamase activity was determined in these isolates. Whole-genome sequencing (WGS) was performed to decipher the role of blaTEM and other genes associated with P/T-R. Changes in the outer membrane protein (OMP) profile were analyzed using SDS-PAGE, and blaTEM and ompC transcription levels were measured by RT-qPCR. In addition, in vitro competition fitness was performed between each pairs of strains (P/T-susceptible vs. P/T-resistant). We found a higher copy number of blaTEM gene in P/T-R isolates, generated by three different genetic events: (1) IS26-mediated duplication of the blaTEM gene, (2) generation of a small multicopy plasmid (ColE-like) carrying blaTEM, and (3) adaptive evolution via reduction of plasmid size, leading to a higher plasmid copy number. Moreover, two P/T-R strains showed reduced expression of OmpC. This study describes the mechanisms involved in the acquisition of P/T-R by E. coli in patients with cIAI. The understanding of P/T-R evolution is crucial for effectively treating infected patients and preventing the spread of resistant microorganisms.
ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17
Authors: Junting Zhang, Yiying Li, Jianchao Zhang, Lu Liu, Yuan Chen, Xusheng Yang, Xueyi Liao, Muhua He, Zihui Jia, Jun Fan, Jin-Song Bian, Xiaowei Nie
Journal: Acta Pharmaceutica Sinica B (2023)

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.
Association between Medicare eligibility at age 65 years and in-hospital treatment patterns and health outcomes for patients with trauma: regression discontinuity approach
Authors: Deepon Bhaumik, Chima D Ndumele, John W Scott, Jacob Wallace
Journal: BMJ (2023)

Abstract Objective To determine whether health systems in the United States modify treatment or discharge decisions for otherwise similar patients based on health insurance coverage. Design Regression discontinuity approach. Setting American College of Surgeons’ National Trauma Data Bank, 2007-17. Participants Adults aged between 50 and 79 years with a total of 1 586 577 trauma encounters at level I and level II trauma centers in the US. Interventions Eligibility for Medicare at age 65 years. Main outcome measures The main outcome measure was change in health insurance coverage, complications, in-hospital mortality, processes of care in the trauma bay, treatment patterns during hospital admission, and discharge locations at age 65 years. Results 1 586 577 trauma encounters were included. At age 65, a discontinuous increase of 9.6 percentage points (95% confidence interval 9.1 to 10.1) was observed in the share of patients with health insurance coverage through Medicare at age 65 years. Entry to Medicare at age 65 was also associated with a decrease in length of hospital stay for each encounter, of 0.33 days (95% confidence interval −0.42 to −0.24 days), or nearly 5%), which coincided with an increase in discharges to nursing homes (1.56 percentage points, 95% confidence interval 0.94 to 2.16 percentage points) and transfers to other inpatient facilities (0.57 percentage points, 0.33 to 0.80 percentage points), and a large decrease in discharges to home (1.99 percentage points, −2.73 to −1.27 percentage points). Relatively small (or no) changes were observed in treatment patterns during the patients’ hospital admission, including no changes in potentially life saving treatments (eg, blood transfusions) or mortality. Conclusions The findings suggest that differences in treatment for otherwise similar patients with trauma with different forms of insurance coverage arose during the discharge planning process, with little evidence that health systems modified treatment decisions based on patients’ coverage.
Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma
Authors: Hidenori Toyoda, Mounika Kanneganti, Jonathan Melendez-Torres, Neehar D. Parikh, Prasun K. Jalal, Federico Piñero, Manuel Mendizabal, Ezequiel Ridruejo, Hugo Cheinquer, Andrea Casadei-Gardini, Arndt Weinmann, Markus Peck-Radosavljevic, Jean-Francois Dufour, Pompilia Radu, Gamal Shiha, Riham Soliman, Shiv K. Sarin, Manoj Kumar, Jing-Houng Wang, Pisit Tangkijvanich, Wattana Sukeepaisarnjaroen, Masanori Atsukawa, Haruki Uojima, Akito Nozaki, Makoto Nakamuta, Koichi Takaguchi, Atsushi Hiraoka, Hiroshi Abe, Kentaro Matsuura, Tsunamasa Watanabe, Noritomo Shimada, Kunihiko Tsuji, Toru Ishikawa, Shigeru Mikami, Ei Itobayashi, Amit G. Singal, Philip J. Johnson
Journal: Clinical Gastroenterology and Hepatology (2023)

Widespread use of direct-acting antivirals for hepatitis C virus infection has been paralleled with increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response (post-SVR HCC) worldwide. Few data compare regional differences in the presentation and prognosis of patients with post-SVR HCC.
Adjuvant endocrine therapy uptake, toxicity, quality of life, and prediction of early discontinuation
Authors: Félix Balazard, Aurélie Bertaut, Élise Bordet, Stéphane Mulard, Julie Blanc, Nathalie Briot, Gautier Paux, Asma Dhaini Merimeche, Olivier Rigal, Charles Coutant, Marion Fournier, Christelle Jouannaud, Patrick Soulie, Florence Lerebours, Paul-Henri Cottu, Olivier Tredan, Laurence Vanlemmens, Christelle Levy, Marie-Ange Mouret-Reynier, Mario Campone, Keri J S Brady, Medha Sasane, Megan Rice, Catherine Coulouvrat, Anne-Laure Martin, Alexandra Jacquet, Ines Vaz-Luis, Christina Herold, Barbara Pistilli
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Many patients receiving adjuvant endocrine therapy (ET) for breast cancer experience side effects and reduced quality of life (QoL) and discontinue ET. We sought to describe these issues and develop a prediction model of early discontinuation of ET. Methods Among patients with hormone receptor–positive and HER2-negative stage I-III breast cancer of the Cancer Toxicities cohort (NCT01993498) who were prescribed adjuvant ET between 2012 and 2017, upon stratification by menopausal status, we evaluated adjuvant ET patterns including treatment change and patient-reported discontinuation and ET-associated toxicities and impact on QoL. Independent variables included clinical and demographic features, toxicities, and patient-reported outcomes. A machine-learning model to predict time to early discontinuation was trained and evaluated on a held-out validation set. Results Patient-reported discontinuation rate of the first prescribed ET at 4 years was 30% and 35% in 4122 postmenopausal and 2087 premenopausal patients, respectively. Switching to a new ET was associated with higher symptom burden, poorer QoL, and higher discontinuation rate. Early discontinuation rate of adjuvant ET before treatment completion was 13% in postmenopausal and 15% in premenopausal patients. The early discontinuation model obtained a C index of 0.62 in the held-out validation set. Many aspects of QoL, most importantly fatigue and insomnia (European Organization for Research and Treatment of Cancer QoL questionnaire 30), were associated with early discontinuation. Conclusion Tolerability and adherence to ET remains a challenge for patients who switch to a second ET. An early discontinuation model using patient-reported outcomes identifies patients likely to discontinue their adjuvant ET. Improved management of toxicities and novel more tolerable adjuvant ETs are needed for maintaining patients on treatment.
Reporting of Harmonising Outcome Measures for Eczema (HOME) core outcome set instruments in randomized clinical trials for systemic treatments in atopic dermatitis
Authors: Megan Lam, Phyllis I Spuls, Yael A Leshem, Louise A A Gerbens, Kim S Thomas, Bernd  Arents, Tim Burton, Carsten Flohr, Aaron M Drucker
Journal: British Journal of Dermatology (2023)

The HOME initiative has successfully completed a core outcome set for atopic dermatitis (AD) trials, and most trials now include the core set instruments. However, to enable evidence synthesis of all relevant trials, reporting must also be standardized. In this study, we evaluated the reporting of the core outcome set instruments in AD systemic treatment trials included in a living systematic review and network meta-analysis. We found that although the core instruments were measured in most trials, they were often not reported sufficiently to enable inclusion in network meta-analysis.
The expanding psoriasis therapeutic landscape: reading and understanding clinical trials
Authors: Niamh Kearney, Brian Kirby
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof The expanding psoriasis therapeutic landscape: reading and understanding clinical trials Get access Niamh Kearney, Niamh Kearney Department of Dermatology, Belfast Health and Social Care Trust, Belfast, UKSchool of Medicine Correspondence: Niamh Kearney. Email: nkearne@tcd.ie https://orcid.org/0000-0002-6469-3462 Search for other works by this author on: Oxford Academic Google Scholar Brian Kirby Brian Kirby School of MedicineDepartment of Dermatology, St Vincent’s University Hospital, Dublin, IrelandCharles Institute of Dermatology, University College Dublin, Ireland https://orcid.org/0000-0001-7596-892X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad238, https://doi.org/10.1093/bjd/ljad238 Published: 12 July 2023 Article history Received: 07 July 2023 Accepted: 08 July 2023 Published: 12 July 2023 Corrected and typeset: 08 August 2023
Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial
Authors: Laurence Albiges, Howard Gurney, Vagif Atduev, Cristina Suarez, Miguel A Climent, David Pook, Piotr Tomczak, Philippe Barthelemy, Jae Lyun Lee, Viktor Stus, Thomas Ferguson, Pawel Wiechno, Erhan Gokmen, Louis Lacombe, Craig Gedye, Rodolfo F Perini, Manish Sharma, Xiang Peng, Chung-Han Lee
Journal: The Lancet Oncology (2023)
Vaccination with <i>Plasmodium vivax</i> Duffy-binding protein inhibits parasite growth during controlled human malaria infection
Authors: Mimi M. Hou, Jordan R. Barrett, Yrene Themistocleous, Thomas A. Rawlinson, Ababacar Diouf, Francisco J. Martinez, Carolyn M. Nielsen, Amelia M. Lias, Lloyd D. W. King, Nick J. Edwards, Nicola M. Greenwood, Lucy Kingham, Ian D. Poulton, Baktash Khozoee, Cyndi Goh, Susanne H. Hodgson, Dylan J. Mac Lochlainn, Jo Salkeld, Micheline Guillotte-Blisnick, Christèle Huon, Franziska Mohring, Jenny M. Reimer, Virander S. Chauhan, Paushali Mukherjee, Sumi Biswas, Iona J. Taylor, Alison M. Lawrie, Jee-Sun Cho, Fay L. Nugent, Carole A. Long, Robert W. Moon, Kazutoyo Miura, Sarah E. Silk, Chetan E. Chitnis, Angela M. Minassian, Simon J. Draper
Journal: Science Translational Medicine (2023)

There are no licensed vaccines against Plasmodium vivax. We conducted two phase 1/2a clinical trials to assess two vaccines targeting P. vivax Duffy-binding protein region II (PvDBPII). Recombinant viral vaccines using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well as a protein and adjuvant formulation (PvDBPII/Matrix-M) were tested in both a standard and a delayed dosing regimen. Volunteers underwent controlled human malaria infection (CHMI) after their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparisons of parasite multiplication rates in the blood. PvDBPII/Matrix-M, given in a delayed dosing regimen, elicited the highest antibody responses and reduced the mean parasite multiplication rate after CHMI by 51% (n = 6) compared with unvaccinated controls (n = 13), whereas no other vaccine or regimen affected parasite growth. Both viral-vectored and protein vaccines were well tolerated and elicited expected, short-lived adverse events. Together, these results support further clinical evaluation of the PvDBPII/Matrix-M P. vivax vaccine.
PTEN deficiency facilitates gemcitabine efficacy in cancer by modulating the phosphorylation of PP2Ac and DCK
Authors: Tian-Yi Jiang, Xiao-Wen Cui, Tian-Mei Zeng, Yu-Fei Pan, Yun-Kai Lin, Xiao-fan Feng, Ye-Xiong Tan, Zhen-gang Yuan, Li-Wei Dong, Hong-Yang Wang
Journal: Science Translational Medicine (2023)

Gemcitabine is a nucleoside analog that has been successfully used in the treatment of multiple cancers. However, intrinsic or acquired resistance reduces the chemotherapeutic potential of gemcitabine. Here, we revealed a previously unappreciated mechanism by which phosphatase and tensin homolog (PTEN), one of the most frequently mutated genes in human cancers, dominates the decision-making process that is central to the regulation of gemcitabine efficacy in cholangiocarcinoma (CCA). By investigating a gemcitabine-treated CCA cohort, we found that PTEN deficiency was correlated with the improved efficacy of gemcitabine-based chemotherapy. Using cell-based drug sensitivity assays, cell line-derived xenograft, and patient-derived xenograft models, we further confirmed that PTEN deficiency or genetic-engineering down-regulation of PTEN facilitated gemcitabine efficacy both in vitro and in vivo. Mechanistically, PTEN directly binds to and dephosphorylates the C terminus of the catalytic subunit of protein phosphatase 2A (PP2Ac) to increase its enzymatic activity, which further dephosphorylates deoxycytidine kinase (DCK) at Ser74 to diminish gemcitabine efficacy. Therefore, PTEN deficiency and high phosphorylation of DCK predict a better response to gemcitabine-based chemotherapy in CCA. We speculate that the combination of PP2A inhibitor and gemcitabine in PTEN-positive tumors could avoid the resistance of gemcitabine, which would benefit a large population of patients with cancer receiving gemcitabine or other nucleoside analogs.